A. Field of the Invention
The present invention relates generally to drug delivery compositions. In particular, this invention relates to the use of liquid bioerodible materials for sustained release of an active agent by injecting to a targeted area of a subject.
B. Background of the Invention
1. Solid Drug Delivery Systems
Current drug delivery treatment options are oftentimes difficult to use and can Is be ineffective due to the inefficient delivery of an active agent to a targeted site. For instance, solid matrix (drug mixed with a solid bioerodable or non-errodable polymer) has to be surgically inserted in the targeted area. Polymers used in this area include polylactic acid, polyglycolic acid, poly ε-caprolactones, polyhydroxybutayrate, polyhydroxybutyrate-polyhydroxyvalerate co-polymers, among others. These polymers typically have high molecular weight typically 10,000 to 100,000 and thus are rigid polymers having high melting points above 70° C.
2. Liquid Drug Delivery Systems
Attempts to make injectable formulations typically involve using a solution of polymers in an organic solvent such as N-methylpyrrolidone (US 2006/0009498). The use of solvents can oftentimes increase the potential toxicity of the drug delivery formulation.
Injectable polymeric systems which are liquid at room temperature and do not require solvents include POE polymers. For instance, U.S. Pat. Nos. 4,079,038, 4,093,709, 4,131,648, 4,138,344 and 4,180,646 disclose drug delivery systems using bioerodible POE polymers. These polymers are formed by a reaction between an orthoester (or orthocarbonate) such as 2,2-diethoxytetrahydrofuran and a diol such as 1,4-cyclohexanedimethanol. The reaction requires elevated temperature and reduced pressure and a relatively long reaction time. Drugs or other active agents are retained in the polymer matrix to be released as the polymer biodegrades due to hydrolysis of the labile linkages. U.S. Pat. No. 4,304,767 discloses POE polymers having repeating units represented by the general formulas:
The polymers are formed by a condensation reaction between ketene acetals and hydroxyl containing compounds and have relatively higher molecular weights. A disadvantage of POE polymers is that they tend to have a relatively fast degradation time. This can render them un-suitable as long-term controlled release drug delivery vehicles.
The use of water-soluble polymers has also been used in liquid drug delivery systems. For instance, U.S. Pat. No. 5,648,506 describes a polymeric drug delivery system where an active agent is bound to a water-soluble polymer to provide a form of soluble drug delivery especially for those cases in which the drug by itself is water -insoluble. In particular, taxol is covalently bound to water-soluble polyethylene glycols with other functional monomers to comprise a form of polymeric drug delivery. A disadvantage of water soluble polymers is that they can induce inflammatory complications in certain ophthalmic treatment applications.